Impact of preexisting interstitial lung disease on mortality in COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study.

BACKGROUND: COVID-19 patients with preexisting interstitial lung disease (ILD) were reported to have a high mortality rate; however, this was based on data from the early stages of the pandemic. It is uncertain how their mortality rates have changed with the emergence of new variants of concern as well as the development of COVID-19 vaccines and treatments. It is also unclear whether having ILD still poses a risk factor for mortality. As COVID-19 continues to be a major concern, further research on COVID-19 patients with preexisting ILD is necessary. METHODS: We extracted data on COVID-19 patients between January 2020-August 2021 from a Japanese nationwide insurance claims database and divided them into those with and without preexisting ILD. We investigated all-cause mortality of COVID-19 patients with preexisting ILD in wild-type-, alpha-, and delta-predominant waves, to determine whether preexisting ILD was associated with increased mortality. RESULTS: Of the 937,758 adult COVID-19 patients, 7,333 (0.8%) had preexisting ILD. The proportion of all COVID-19 patients who had preexisting ILD in the wild-type-, alpha-, and delta-predominant waves was 1.2%, 0.8%, and 0.3%, respectively, and their 60-day mortality was 16.0%, 14.6%, and 7.5%, respectively. The 60-day mortality significantly decreased from the alpha-predominant to delta-predominant waves (difference - 7.1%, 95% confidence intervals (CI) - 9.3% to - 4.9%). In multivariable analysis, preexisting ILD was independently associated with increased mortality in all waves with the wild-type-predominant, odds ratio (OR) 2.10, 95% CI 1.91-2.30, the alpha-predominant wave, OR 2.14, 95% CI 1.84-2.50, and the delta-predominant wave, OR 2.10, 95%CI 1.66-2.66. CONCLUSIONS: All-cause mortality rates for COVID-19 patients with preexisting ILD decreased from the wild-type- to the more recent delta-predominant waves. However, these patients were consistently at higher mortality risk than those without preexisting ILD. We emphasize that careful attention should be given to patients with preexisting ILD despite the change in the COVID-19 environment.

Nationwide survey of adult patients with pulmonary alveolar proteinosis using the National Database of designated intractable diseases of Japan.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) and congenital/hereditary PAP were labeled intractable diseases in Japan in 2015. Since then, patients registered in the National Database of Designated Incurable Diseases (NDDID) who met certain requirements became eligible for medical subsidies. Epidemiological studies using recent data are needed for the development of management protocols for patients with PAP. METHODS: We conducted the first nationwide study describing the epidemiology and characteristics of PAP using data for patients registered in the Japanese NDDID between 2015 and 2020. We focused on patient demographics, diagnosis, disease severity score (DSS), symptoms, test results, and treatment. RESULTS: We identified 110 patients with PAP, among whom 96.4% had APAP/idiopathic PAP (IPAP). The median age was 58 years, with a slight male predominance. Most patients had a DSS ≥3 (64.5%) and reported symptoms (e.g., dyspnea on exertion). High-resolution computed tomography typically revealed ground glass opacity and crazy paving appearances. Pulmonary function was relatively preserved, except for carbon monoxide diffusing capacity. Only 27.4% of patients underwent therapeutic whole-lung lavage and/or bronchoalveolar lavage, while 25% required long-term oxygen therapy. Serum Krebs von den Lungen-6, surfactant protein D, and lactate dehydrogenase levels significantly and positively correlated with the DSS. CONCLUSIONS: Most patients registered in the NDDID have APAP/IPAP with a DSS ≥3, and about one-quarter require long-term oxygen therapy and infrequent lavages. Our results provide important details of the current prevalence and clinical practice related to APAP/IPAP with a DSS ≥3 in Japan.

Sporadic Myotonic Dystrophy Type 2 in a Japanese Patient.

We herein report a Japanese patient with myotonic dystrophy type 2 (DM2), which is rare in Japan. A 64-year-oldman had proximal muscle weakness and grip myotonia. Electromyography showed myotonic discharges, but dystrophia-myotonica protein kinase (DMPK) was negative for CTG repeats. A muscle biopsy revealed increased central nuclei, pyknotic nuclear clumps and muscle fiber atrophy, mainly in type 2 fibers, raising the possibility of DM2. The diagnosis was genetically confirmed by the abnormal CCTG repeat size in cellular nucleic acid-binding protein (CNBP) on repeat-primed polymerase chain reaction, which was estimated to be around 4,500 repeats by Southern blotting.

Intra-abdominal Hemorrhage Due to Splenic Vein Aneurysm Rupture Caused by Invasive Aspergillosis during Treatment for Advanced Non-small-cell Lung Cancer.

A 71-year-old man was admitted for left-sided chest pain. He had a history of diabetes, treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small-cell lung cancer, and corticosteroid treatment for underlying lung diseases. Chest computed tomography showed consolidations in the bilateral lower lobes, and Aspergillus fumigatus was detected by bronchoscopy. Invasive pulmonary aspergillosis was suspected, and antifungal therapy with voriconazole was initiated; however, the patient passed away suddenly. Autopsy revealed disseminated Aspergillus infection and intra-abdominal hemorrhage due to the rupture of a splenic vein aneurysm caused by Aspergillus necrotizing vasculitis, which was considered the cause of death.

Changes in the characteristics and outcomes of COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study.

The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed because of virus mutations, vaccine dissemination, treatment development and policies, among other factors. These factors have a dynamic and complex effect on the characteristics and outcomes of patients. Therefore, there is an urgent need to understand those changes and update the evidence. We used a large-scale real-world data set of 937,758 patients with COVID-19 from a nationwide claims database that included outpatients and inpatients in Japan to investigate the changes in their characteristics, outcomes and risk factors for severity/mortality from the early pandemic to the delta variant-predominant waves. The severity of COVID-19 was defined according to the modified World Health Organization clinical-progression ordinal scale. With changing waves, mean patient age decreased, and proportion of patients with comorbidities decreased. The incidences of "severe COVID-19 or death (i.e. ≥severe COVID-19)" and "death" markedly declined (5.0% and 2.9%, wild-type-predominant; 4.6% and 2.2%, alpha variant-predominant and 1.4% and 0.4%, delta variant-predominant waves, respectively). Across the wave shift, risk factors for ≥ severe COVID-19 and death, including older age, male, malignancy, congestive heart failure and chronic obstructive pulmonary disease, were largely consistent. The significance of some factors, such as liver disease, varied as per the wave. This study, one of the largest population-based studies on COVID-19, showed that patient characteristics and outcomes changed during the waves. Risk factors for severity/mortality were similar across all waves, but some factors were inconsistent. These data suggest that the clinical status of COVID-19 will change further with the coming epidemic wave.

Relationship of brain edema after deep brain stimulation surgery with motor and cognitive function.

Background: Some patients with Parkinson's disease (PD) develop peri-lead brain edema after deep brain stimulation (DBS) surgery. The influence of edema on neurological function is not well characterized. We investigated the relationship of brain edema after DBS surgery with motor and cognitive function. Methods: Thirteen patients with PD (6 males and 7 females; mean age: 61.2 years) who underwent bilateral subthalamic nucleus (STN) DBS surgery were included. All patients underwent magnetic resonance imaging (MRI) examination on day 6 post-DBS surgery. The volume of edema was measured either in the frontal white matter or STN on fluid attenuated inversion recovery (FLAIR) images. We examined the relationship between these volumes and changes in cognitive and motor function. Results: Patients were divided into those with frontal subcortical edema (FE) ≥3,000 mm3 (FE + group; n = 7) and <3,000 mm3 (FE-group; n = 6). In the FE + group, the postoperative Mini-Mental State Examination score worsened by 2.4 points after one week compared with that immediately before surgery, while that in the FE-group worsened only by 0.2 points (p = 0.038). On comparing patients with peri-STN edema (SE) ≥1,000 mm3 (SE + group; n = 3) and those with SE < 1,000 mm3 (SE-group; n = 10) showed that frequency of DBS tuning in the early postoperative period of the SE + group was lesser than that in the SE-group. Conclusions: Development of FE after DBS surgery was related to transient cognitive decline. On the other hand, SE seemed associated with altered motor function and reduces the requirement for tuning in the initial period after DBS implantation.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with uncommon histology: a propensity-score-matched analysis.

BACKGROUND: Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown. METHODS: Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups. RESULTS: Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8-7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4-27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1-7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6-29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC. CONCLUSIONS: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.

Long-term MRI changes in a patient with Kelch-like protein 11-associated paraneoplastic neurological syndrome.

BACKGROUND AND PURPOSE: The aim of this study was to identify the long-term radiological changes, autoantibody specificities, and clinical course in a patient with kelch-like protein 11 (KLHL11)-associated paraneoplastic neurological syndrome (PNS). METHODS: Serial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage-display ImmunoPrecipitation and Sequencing (PhIP-Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue. RESULTS: A 42-year-old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a "hot-cross-bun sign", and low-signal intensity on susceptibility-weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP-Seq enriched for KLHL11-derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co-localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti-KLHL11 antibody-positive particles in cytoplasm. CONCLUSIONS: This study suggests that KLHL11-PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2-FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.

Prognostic significance of bronchoalveolar lavage cellular analysis in patients with acute exacerbation of interstitial lung disease.

BACKGROUND: Acute exacerbation (AE) of interstitial lung disease (ILD) is an acute respiratory deterioration of unknown etiology, associated with high mortality. Currently, bronchoalveolar lavage (BAL) has been no longer required for the diagnosis of AE-ILD; however, the clinical utility of BAL fluid (BALF) cellular analysis in AE-ILD remains unclear. METHODS: A retrospective study of 71 patients who underwent BAL at our institution between 2005 and 2019 and were diagnosed with AE-ILD was conducted. We performed BALF cellular analysis and evaluated its prognostic significance. RESULTS: There were 26 patients with AE of idiopathic pulmonary fibrosis (IPF) and 45 with AE of non-IPF, including idiopathic interstitial pneumonias/non-IPF (n = 22), ILD associated with collagen tissue disease (n = 20) and fibrotic hypersensitivity pneumonia (n = 3). All patients were treated with high-dose corticosteroids, and the 90-day mortality after AE was 31%. Most patients showed a high percentage of lymphocytes and/or neutrophils in BALF regardless of the underlying ILD. There was a significant negative correlation between BALF neutrophils and the PaO2/FiO2 ratio, and patients with UIP pattern or diffuse AE pattern on HRCT had a significantly higher percentage of BALF neutrophils than those with other patterns. Multivariate analysis revealed that lower and higher percentage of lymphocytes and neutrophils, respectively, in BALF were independent poor prognostic factors for 90-day survival. BALF lymphocyte and neutrophil count ≥25% and <20%, respectively, predicted favorable survival after AE. CONCLUSIONS: Cellular analysis of BALF in AE-ILD is a potential biomarker for predicting prognosis after AE.

Significance of Brain Imaging for Staging in Patients With Clinical Stage T1-2 N0 Non-Small-Cell Lung Cancer on Positron Emission Tomography/Computed Tomography.

BACKGROUND: Routine positron emission tomography/computed tomography (PET/CT) has been recommended even for clinical stage I non-small-cell lung cancer (NSCLC). In spite of the progress in the screening procedure, and revisions to TNM classification, there is no evidence to support brain imaging screening of patients assessed with the current staging protocol including PET/CT. MATERIALS AND METHODS: We retrospectively investigated the frequency of extrathoracic metastasis in 466 consecutive patients with clinical stage T1-2 N0 NSCLC with the complete staging assessment comprised of thin-section CT, PET/CT, and brain contrast-enhanced magnetic resonance imaging between 2008 and 2016. All patients were reclassified according to the eighth edition of the tumor, node, and metastasis (TNM) classification. RESULTS: Among all patients, 70% of the tumors were pure solid and 30% had part-solid ground-glass opacity on thin-section CT, and 388 (83%) and 78 (17%) were classified into clinical stages T1 and T2, respectively. Eight patients (1.7%) had extrathoracic metastasis, including 3 (0.6%) with brain metastasis, and all showed pure-solid tumors. The frequency of extrathoracic and brain metastasis was 1.0% and 0.5% in 388 T1 patients, and 5.0% and 3.0% in 78 T2 patients. Although brain metastases were detected in 2 of 7 patients (29%) with PET/CT detectable extrathoracic metastases and 1 of 459 patients (0.2%) without PET/CT detectable extrathoracic metastasis, there were no neurologically asymptomatic brain metastases in patients with early-stage NSCLC confirmed by PET/CT. CONCLUSION: Routine screening of brain imaging is unnecessary in patients with early-stage NSCLC, assessed with the current staging protocol including PET/CT.

Neuromelanin-sensitive magnetic resonance imaging in disease differentiation for parkinsonism or neurodegenerative disease affecting the basal ganglia.

INTRODUCTION: Several reports have shown that neuromelanin-sensitive magnetic resonance imaging (NMI) using 3T magnetic resonance imaging is useful for the differential diagnosis of Parkinson's disease (PD), progressive supranuclear palsy (PSP), and other neurological diseases. However, the number of cases in previous studies has been insufficient. We aimed to determine the relationship between NMI and severity of PD and related disorders, and thereby establish the diagnostic utility of NMI for diagnosing neurological diseases. METHODS: We enrolled 591 patients (531 subjects after removal of duplicates) with parkinsonism who underwent NMI. The contrast ratio of the locus coeruleus (LC-CR) and the area of the substantia nigra pars compacta (SNc) were analyzed in each patient. RESULTS: The patients' clinical diagnoses were as follows: 11 patients in the disease control group (DCG), 244 patients with PD, 49 patients with PSP, and 19 patients with multiple system atrophy with predominant parkinsonism. Additionally, some patients were diagnosed with dementia with Lewy bodies, vascular parkinsonism, and drug-induced parkinsonism. SNc in the patients with PD and PSP was significantly smaller than that in DCG. LC-CR in the patients with PD was lower than that in DCG; furthermore, LC-CR in the patients with PD was significantly lower than that in the patients with PSP. We found that an area under the receiver-operating characteristic curve, indicating diagnostic efficacy, of 0.85 for LC-CR is a promising biomarker for differentiating PD from PSP. CONCLUSION: NMI effectively contributes to differentiating neurodegenerative diseases, such as PD and PSP.

Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: a multicentre retrospective cohort study.

Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is a major prognostic determinant. However, evidence for its prognostic strength is mainly based on the results of small cohort studies with statistical limitations. This retrospective study, which included 108 patients with a first episode of AE-IPF, aimed to identify prognostic factors and to develop prognostic classification models. Multivariate Cox regression analysis revealed that a lower percent-predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and a lower PaO2/FiO2 ratio at AE onset were independent mortality predictors. If the value of each predictor was lower than the cutoff determined by receiver-operating characteristic analysis, 1 point was assigned. Classification of patients into mild, moderate, and severe groups based on total score showed post-AE 90-day cumulative survival rates of 83.3%, 66.2%, and 22.2%, respectively (model 1: C-index 0.702). Moreover, a decision tree-based model was created with the recursive partitioning method using baseline %FVC and PaO2/FiO2 ratio at AE onset from among multivariable; accordingly, patients were classified into 3 groups with post-AE 90-day cumulative survival rates of 84.1%, 64.3%, and 24.0%, respectively (model 2: C-index 0.735). These models can guide clinicians in determining therapeutic strategies and help design future studies on AE-IPF.

Risk Factors for Pneumonia and Death in Adult Patients With Seasonal Influenza and Establishment of Prediction Scores: A Population-Based Study.

BACKGROUND: Seasonal influenza remains a global health problem; however, there are limited data on the specific relative risks for pneumonia and death among outpatients considered to be at high risk for influenza complications. This population-based study aimed to develop prediction models for determining the risk of influenza-related pneumonia and death. METHODS: We included patients diagnosed with laboratory-confirmed influenza between 2016 and 2017 (main cohort, n = 25 659), those diagnosed between 2015 and 2016 (validation cohort 1, n = 16 727), and those diagnosed between 2017 and 2018 (validation cohort 2, n = 34 219). Prediction scores were developed based on the incidence and independent predictors of pneumonia and death identified using multivariate analyses, and patients were categorized into low-, medium-, and high-risk groups based on total scores. RESULTS: In the main cohort, age, gender, and certain comorbidities (dementia, congestive heart failure, diabetes, and others) were independent predictors of pneumonia and death. The 28-day pneumonia incidence was 0.5%, 4.1%, and 10.8% in the low-, medium-, and high-risk groups, respectively (c-index, 0.75); the 28-day mortality was 0.05%, 0.7%, and 3.3% in the low-, medium-, and high-risk groups, respectively (c-index, 0.85). In validation cohort 1, c-indices for the models for pneumonia and death were 0.75 and 0.87, respectively. In validation cohort 2, c-indices for the models were 0.74 and 0.87, respectively. CONCLUSIONS: We successfully developed and validated simple-to-use risk prediction models, which would promptly provide useful information for treatment decisions in primary care settings.

Prognosis after acute exacerbation in patients with interstitial lung disease other than idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation (AE) is recognized as a life-threatening condition with acute respiratory worsening in idiopathic pulmonary fibrosis (IPF). AE also occurs in fibrotic interstitial lung disease (ILD) other than IPF, including other types of idiopathic interstitial pneumonias (IIPs), ILD associated with collagen vascular disease (CVD-ILD), and chronic hypersensitivity pneumonia (CHP). However, the clinical impact after AE in those patients is still unclear. METHODS: A retrospective review of 174 consecutive first-episodes with AE of ILD in our institution from 2002 to 2016 was performed. AE was defined according to the revised definition and diagnostic criteria proposed by an international working group in 2016. Clinical characteristics, 90-day survival, and the requirement of long-term oxygen therapy (LTOT) after AE were evaluated in each underlying ILD. RESULTS: There were 102 patients with AE of IPF (AE-IPF) and 72 with AE of ILD other than IPF, including non-IPF IIPs (n = 29) and secondary ILD (n = 43) [CVD-ILD (n = 39), CHP (n = 4)]. In CVD-ILD, rheumatoid arthritis (n = 17) was most common. The 90-day mortality after AE was 57% in IPF, 29% in non-IPF IIPs, and 33% in secondary ILD. After AE, ILD other than IPF had a significantly better survival rate than IPF (P < 0.001). Among survivors, the rates of patients requiring LTOT after AE were 63% in IPF, 35% in non-IPF IIPs, and 46% in secondary ILD, respectively. CONCLUSIONS: AE of ILD other than IPF might have a better prognosis than AE-IPF, but both are fatal conditions that cause chronic respiratory failure.

[Dermatomyositis with squamous cell carcinoma of the lungs secondary to nivolumab treatment: a case report].

A 74-year-old man was administered nivolumab to treat recurrent squamous cell carcinoma of the lungs. He developed fatigue, redness on the front of his neck, muscle weakness, and difficulty in swallowing after receiving the third course of nivolumab. Physical and neurological examinations showed proximal limb muscle weakness, periorbital erythema, and erythema of the front of his neck as well as fingers. Laboratory investigations revealed elevated serum CK and aldolase levels, and he was diagnosed with dermatomyositis. We initiated steroid pulse therapy and intravenous immunoglobulin therapy; however, he died of advanced lung cancer. Immune checkpoint inhibitor-induced neuromuscular disease is increasingly being observed in clinical practice. We report a rare case of dermatomyositis with squamous cell carcinoma of the lungs secondary to nivolumab treatment.

Prognostic impact of an early marginal decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone.

BACKGROUND: Pirfenidone (PFD), an oral antifibrotic drug, is conditionally recommended for the treatment of idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the prognostic factors in IPF patients treated with PFD and clarify the clinical significance of marginal physiological changes after PFD therapy. METHODS: We retrospectively reviewed 96 consecutive IPF patients treated with PFD. The physiological evaluation was performed at 3-6 months after PFD therapy, and the findings were classified into three groups based on the presence of a 5% change in %forced vital capacity (%FVC): improved, stable, and worsened. The clinical characteristics and prognostic outcomes were compared among groups, and the prognostic factors were evaluated by Cox proportional hazards analysis. RESULTS: Of the 96 patients, 25 (26.0%) showed acute exacerbation (AE) and 40 (41.6%) died during the observation period (median, 17 months). Physiological responses could be evaluated in 80 patients and the findings were as follows: improved, 23%; stable, 36%; and worsened, 41%. Time to the first AE and the survival rate were significantly shorter and lower, respectively, in the worsened group than in the improved/stable group (P = 0.002, P < 0.001, respectively). The prognostic analysis revealed that low %FVC at baseline (hazard ratio [HR]: 0.973 [0.950-0.996]), use of supplemental oxygen (HR: 2.180 [1.041-4.622]), and a "worsened" status after PFD therapy (HR: 5.253 [2.541-11.400]) were significantly associated with a poor prognosis. CONCLUSIONS: An early marginal decline in FVC may be important for survival outcomes in PFD-treated IPF patients.

Clinical significance of lower-lobe interstitial lung disease on high-resolution computed tomography in patients with idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare form of idiopathic interstitial pneumonias (IIP) and may have other patterns of interstitial lung disease (ILD) in the lower lobe, such as usual interstitial pneumonia (UIP). However, the clinical significance of lower-lobe ILD in patients with IPPFE is unclear. METHODS: A retrospective review of 40 consecutive patients with clinically diagnosed IPPFE in our institution from 2005 to 2016 was conducted. The presence of lower-lobe ILD on high-resolution computed tomography (HRCT) was assessed and classified into UIP or non-UIP pattern according to a modification of diagnostic criteria for idiopathic pulmonary fibrosis. Clinical characteristics and prognostic factors were evaluated. RESULTS: Among the 40 patients with IPPFE, 21 (53%) had lower-lobe ILD, including 13 with UIP pattern and 8 with non-UIP pattern. Patients with IPPFE who had lower-lobe ILD had significantly older age, higher frequency of fine crackles, higher serum KL-6 level, lower residual volume (RV), and lower total lung capacity (TLC) than those without lower-lobe ILD. In addition, those with lower-lobe ILD, especially UIP pattern, had a significantly poorer survival than those without lower-lobe ILD (log-rank test; p = 0.014, p < 0.001, respectively). Multivariate Cox proportional hazards regression analysis revealed that low %forced vital capacity (%FVC) at baseline and coexistence of UIP pattern were significantly associated with poor prognosis in patients with IPPFE. CONCLUSIONS: The coexistence of lower-lobe ILD on HRCT, especially the UIP pattern, may predict poor survival in patients with IPPFE.

Efficacy of corticosteroid and intravenous cyclophosphamide in acute exacerbation of idiopathic pulmonary fibrosis: A propensity score-matched analysis.

BACKGROUND AND OBJECTIVE: Acute exacerbation (AE) is a leading cause of death in patients with idiopathic pulmonary fibrosis (IPF). Although optimal treatment for AE-IPF remains unclear, high-dose corticosteroids (CS) with/without immunosuppressants, including intravenous cyclophosphamide (IVCY), are often used as empirical therapy. However, the survival benefit of adding IVCY to CS therapy is unknown. We investigated the efficacy of this therapy in patients with AE-IPF. METHODS: Overall, 102 consecutive patients with IPF with a first idiopathic AE were included. Post-AE survival rates and treatment safety were retrospectively assessed. Efficacy of CS + IVCY therapy for the first AE was compared with that of CS monotherapy using a propensity score-matched analysis. RESULTS: The post-AE 90-day survival rate of the entire cohort was 64.7%. On the basis of the propensity scores, 26 matched patient pairs were made. Characteristics of matched patients with AE-IPF treated with CS (matched CS group) and those with CS + IVCY (matched CS + IVCY group) were well balanced. No significant between-group differences were observed in post-AE 90-day survival rates (84.6% vs 76.9%; P = 0.70), cumulative survival rates (P = 0.57 by log-rank test) or incidence of adverse events ≥ CTCAE (Common Terminology Criteria for Adverse Events) v5.0 grade 3 (61.5% vs 65.4%; P = 1.00). CONCLUSION: The propensity score-matched analysis demonstrated that compared with CS monotherapy, CS + IVCY therapy did not significantly improve post-AE survival in patients with AE-IPF. Further studies are warranted to assess the efficacy of CS + IVCY therapy for AE-IPF.

IgG4-related disease presenting with combined pulmonary fibrosis and emphysema (CPFE).

A 64-year-old man was admitted to our hospital with an abnormal chest shadow. The patient was a current-smoker and had a past illness of autoimmune pancreatitis with a high serum level of IgG4, 348 mg/dL. Chest CT showed upper-lobe emphysema, and lower-lobe reticulation with honeycombing, suggestive of combined pulmonary fibrosis with emphysema (CPFE). Surgical lung biopsy was revealed a usual interstitial pneumonia pattern with marked infiltration of IgG4-positive plasma cells. The patient was diagnosed with IgG4 related disease (IgG4-RD) presenting with CPFE. Pulmonary manifestation was improved by corticosteroid therapy. IgG4-RD may be an underlying condition in patient with CPFE.

Disseminated Mycobacterium avium Infection Presenting with Bladder Lesions in a Patient with Interferon-γ-neutralizing Autoantibodies.

A 63-year-old woman presented with a fever, eruption, and sterile pyuria. A cystoscopic examination revealed submucosal nodular lesions in the trigone of the bladder, and a biopsy specimen showed epithelioid cell granulomas in the lamina propria of the bladder. Mycobacterium avium grew in the urine culture. Other organ involvement, such as the lungs, spleen, bones, muscles, and pelvic lymph nodes, was observed on radiological examinations, and M. avium was isolated from some organ lesions. Interferon-γ-neutralizing autoantibodies were detected in the patient's serum. Therefore, the patient was diagnosed with disseminated M. avium infection, which was resolved with antimycobacterial treatment.